Recent advances in systemic therapies and radiotherapy for gallbladder cancer

Adjuvant treatment is not routine following resection for gallbladder cancer as most regimens have low response rates. In the palliative setting, recent advances have been made regarding combination chemotherapies and both gemcitabine/cisplatin and gemcitabine/oxaliplatin appear to be superior to single-agent 5FU, which has very little efficacy in this disease. There are isolated reports of dramatic responses to targeted monoclonal agents. The role of radiotherapy has recently been revisited, however, its effectiveness when patients are adequately surgically treated remains to be demonstrated.     

How common is polycystic ovary syndrome in recurrent miscarriage?

The association between polycystic ovary syndrome (PCOS) and recurrent miscarriage (RM) has been long established, but the relative importance of this condition as a cause of RM is far from clear. Previous studies on the prevalence of PCOS in RM have been hampered by a lack of objective and universally accepted criteria for the diagnosis of PCOS, resulting in considerable controversy. However, the Rotterdam criteria have since been accepted as the gold standard for diagnosis of PCOS, and therefore these criteria have been used to produce a much clearer and more objective assessment of the prevalence of PCOS in RM. Three hundred women with recurrent miscarriage were studied. A diagnosis of PCOS was established via measurement of cycle length and day 21 serum progesterone, determination of the free androgen index and pelvic ultrasonography. All ultrasound reports prior to publication of the Rotterdam criteria were reviewed, ensuring consistency in the diagnosis of a polycystic ovary. Ultrasound scans of 27 patients confirmed polycystic ovaries with a further 10 scans suggestive of polycystic ovaries, but with insufficient information for the Rotterdam criteria to be applied. Hence, 27–37 (9.0–12%) patients presented with ultrasonographic polycystic ovaries. Using the Rotterdam criteria, 25–30 (8.3–10%) patients had PCOS. It is concluded that the prevalence of PCOS in RM is considerably lower than has previously been accepted.     

Treatment of recurrent miscarriage and antiphospholipid syndrome with low-dose enoxaparin and aspirin

The aim of this retrospective, observational study was to determine the impact of low-dose enoxaparin (20 mg) in conjunction with low-dose aspirin on the pregnancy outcome of women with antiphospholipid syndrome and recurrent miscarriage. The study was conducted in a tertiary referral teaching hospital. A total of 35 women with antiphospholipid syndrome were treated with low-dose enoxaparin and aspirin as soon as pregnancy was confirmed. The outcome of pregnancy was analysed. The miscarriage rate was 7/35 (20%) whereas the live birth rate was 28/35 (80%). In conclusion, low-dose (20 mg) enoxaparin in conjunction with low-dose aspirin treatment produced encouraging results. The findings in this study suggest that there is a case for randomized controlled trials to compare low-dose (20 mg) enoxaparin with higher doses.     

A stochastic model for cancer stem cell origin in metastatic colon cancer

Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.     

Specificity and mechanism of the histone methyltransferase Pr-Set7

Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific.     

Glomus tympanicum chemodectomas: radiographic and clinical characteristics

Glomus tympanicum chemodectomas are benign neoplasms that develop from normal glomus bodies located along the Jacobson (tympanic) nerve in the middle ear. The medical charts and radiographic studies of 55 patients with these tumors were reviewed. Women outnumbered men in a ratio of 3.5:1, and the patients' average age when they initially reported symptoms was 52 years. Tinnitus, ear pulsations, and diminished hearing were the most frequent symptoms. No patient had a second chemodectoma, and none of seven patients who were tested had elevated neuroendocrine compounds. Review of the radiographic examinations showed that direct coronal, thin-section computed tomography (CT) was the most sensitive means of demonstrating glomus tympanicum chemodectomas. Magnification angiography was also a sensitive diagnostic study, typically depicting a trapezoidal, hypervascular, middle-ear mass that appeared initially in the middle-to-late arterial phase and quickly disappeared in the venous phase. Differentiation from an aberrant internal carotid artery is critical to prevent arterial biopsy.